The activity of medial septal neurons in working memory
The medial septum (MS) is one of the main basal forebrain nuclei and is essential for the generation of hippocampal theta oscillations, a network activity that is crucial for episodic learning and declarative memory. Specifically, lesion and pharmacological studies have demonstrated its importance in spatial memory and navigation. However, most commonly applied rodent navigation tasks involve a working memory (WM) component that may complicate the interpretation of the results (e.g. remembering the previously visited maze arm, or retaining the direction to follow given a certain sensory cue). Moreover, the MS contains heterogeneous cell populations of cholinergic, GABAergic and glutamatergic neurons, and the precise contribution of these cell types to memory processes is not well understood.To address these issues, we have developed a self-initiated 2-alternative forced choice WM task, in which an auditory cue indicates which of two water ports will deliver reward. We eliminated most navigational components by placing the ports close to each other, and instead of requiring the animal to memorize the rewarded direction while moving, enforcing a fixation period before choice. We recorded multiple single neuron activity from the MS using custom-built tetrode micro-drives and attempted optogenetic tagging of cholinergic neurons while mice were performing this task. Preliminary results show distinct activity of MS neurons during the fixation period as well as in response to multiple behaviorally relevant task events, suggesting a specific involvement of the MS in working memory. These experiments may help disentangle navigation and WM-related activity in the basal forebrain.